Abstract 5115: An orthotopic lung tumor model for image-guided microirradiation in rats

Abstract

Abstract Introduction: Studies have confirmed that a new lung cancer treatment called stereotactic body radiation therapy (SBRT) can cure certain patients with early stage tumors situated peripherally in their lungs, using a non-invasive, outpatient procedure. While nearly curative for peripheral lung tumors, SBRT also may present life-threatening toxicity for patients with centrally located lung tumors. Moreover, large, hypoxic tumors are at a further risk of radiotherapy failure with SBRT. The efficacy of SBRT application can be improved through the addition of agents designed to sensitize the tumor and/or protect normal tissue. To investigate and validate the response to SBRT, alone or in combination with radiomodulating compounds, it is necessary to develop a tumor model for image-guided high-dose irradiation of rodent tumors and normal tissues in a manner that closely mimics delivery of SBRT in humans. Therefore, the purpose of this study was to develop a rat orthotopic lung tumor model with a solitary intrapulmonary nodule to study the effects of high-dose radiation. Methods: Adult female athymic nude rats were anesthetized, intubated and then placed on a ventilator (Inspira, Harvard Apparatus, Holliston, MA) prior to surgery. A small incision (1.0 cm) was made between ribs 5 and 6 on the right side. The right lung was captured using a forceps, clamped with a carotid clamp and H460-luc/A549-luc NSCLC cells (one million cells and matrigel in 20 μl) were then injected into the right lung. The tumor growth was monitored by in vivo bioluminescent imaging (BLI) weekly. Other imaging modalities, including microCT, CBCT, and MRI, were also performed. At the end of study, the rats were sacrificed and lungs were harvested to confirm tumor location and size. Results: We achieved 100% survival from this surgical orthotopic implantation procedure. We also achieved >90% success in generating solitary lung tumors in the rats, whereas percutaneous orthotopic injection of tumor cells/chunks in our previous model met only 50 to 60% success in producing solitary tumors. Conclusion: This study presents a successful solitary lung tumor model in rodents which provides investigators a useful model to apply conformal radiation treatment, using a sophisticated treatment planning system and significantly preventing normal tissue damage. Citation Format: Zhang Zhang, Michelle Wodzak, Olivier Belzile, Heling Zhou, Ralph Mason, Rolf Brekken, Rajiv Chopra, Michael D. Story, Robert Timmerman, Debabrata Saha. An orthotopic lung tumor model for image-guided microirradiation in rats. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5115. doi:10.1158/1538-7445.AM2015-5115